The importance of biocompatible and/or biodegradable polymers as carriers for active therapeutic agents is well established. Biocompatible, biodegradable, and relatively inert polymers such as poly(lactide) (PL) or poly(lactide-co-glycolide) (PLGA) containing a bioactive agent are commonly utilized in controlled-release delivery systems (for review, see M. Chasin, Biodegradable polymers for controlled drug delivery. In: J. O. Hollinger Editor, Biomedical Applications of Synthetic Biodegradable Polymers CRC, Boca Raton, Fla. (1995), pp. 1-15; T. Hayashi, Biodegradable polymers for biomedical uses. Prog. Polym. Sci. 19 4 (1994), pp. 663-700; and Harjit Tamber, Pal Johansen, Hans P. Merkle and Bruno Gander, Formulation aspects of biodegradable polymeric microspheres for antigen delivery, Advanced Drug Delivery Reviews, Volume 57, Issue 3, 10 Jan. 2005, Pages 357-376).
With respect to the delivery of therapeutic peptides in particular, however, there still exist many challenges to the design of effective controlled-release, polymer-based delivery systems. A basic requirement for such delivery systems is appropriate control over the release of the encapsulated active agent, an objective which is complicated by variations in the release kinetics of polymer systems. Generally, an initial diffusional or burst release phase from the intact polymer system is followed by a slower lag phase leading to an erosional release phase as the polymer system begins to degrade. It is important to maintain the concentration of the peptide molecule within a therapeutically effective window throughout both of the principal peptide release phases and to avoid excessive concentrations, and particularly an initial burst during the diffusional release phase, which may lead to adverse side effects or untoward results. In this respect, however, wide variation in the size, charge and conformation of different peptide molecules has thus far prevented a more uniform approach to their effective encapsulation.
The prior art describes various strategies for improving controlled-release delivery from polymer-based delivery systems including the use of new polymeric materials and polymer blends, and/or the incorporation of additives in such systems to help facilitate drug release. U.S. Pat. No. 7,326,425, for example, describes a blended polymer-based delivery system having a first polymer capable of forming hydrogen bonds with a desired bioactive agent to prevent bursts, and a second polymer the degradation products of which trigger the release of the active agent from the first polymer. Alternatively, U.S. Patent Publication No. 2007/0092574 describes the addition of certain organic ions to polymer-based delivery systems encapsulating water-soluble bioactive agents to reduce the burst release and degradation of the bioactive agent, wherein the organic ion is selected to neutralize the overall charge of a particular bioactive agent.
In each of these examples, however, and in the prior art in general, the primary focus of such strategies is on manipulation of the polymer-based delivery system to suit the requirements of a particular bioactive agent, as opposed to manipulation or adaptation of the bioactive agent itself.